Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0048—Eye, e.g. artificial tears
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
  • A61P27/12—Ophthalmic agents for cataracts

Definitions

• the present invention relates to a novel composition which is useful for debridement of retained lens materials such as lens epithelial cells by an aspiration during a cataract surgery.
• Cataract frequently in aged people, is an intractable eye disease and various studies on a treatment of cataract have been made. But at present, the treatment of cataract is finally attained by surgical operations. Cataract surgery has been applied for a long time and various operative methods have been examined. In such operative methods, there are problems how to easily and completely extract an opaque lens, how to prevent postoperative complications, and how to fast and satisfactorily recover from operative damages.
• the procedure consists of applying supersonic waves to the cataract in a lens capsule to emulsify it and removing it by aspiration.
• the procedure has merits that complications caused by a large incision are few and the recovery from operation damages is fast because the incised wound is small.
• the phacoemulsification procedure is very useful to extract an opaque lens, however, it needs high technology to remove the retained lens materials such as lens epithelial cells without damaging intraocular tissues.
• Lens epithelial cells have self-proliferating abilities. If the cells remain after an operation, they cause postoperative complications such as secondary cataract, residual capsular opacification, intraocular lens dislocation, fibrin reaction and phacoanaphylactic endophthalmitis. They can be prevented by thorough removal of the lens epithelial cells.
• EDTA ethylenediaminetetraacetic acid
• a posterior chamber intraocular lens may dislocate or luxate. If zonules are dissolved completely, an implantation of an intraocular lens becomes impossible because a sustaining tissue, namely a lens capsule, disappears. Even if an intraocular lens can be implanted, there exists a high risk to dislocate after an operation. Therefore, it needs to study how to keep EDTA in the lens capsule, namely, how to prevent the leakage of EDTA from the capsular opening incised to remove the cataracts.
• the object of the present invention is to provide a method for treating cataract for debridment of retained lens epithelial cells without leakage of EDTA or salts thereof from anterior capsular opening that is needed for removing cataract.
• the other object of this invention is to provide a pharmaceutical composition which is used in above mentioned treating method.
• the inventors having strenuously studied to achieve the above-mentioned object, have found the fact that when EDTA or salts thereof and viscoelastic material both dissolved in a physiologically acceptable solution are injected into the capsular bag after cataract extraction by endocapsular phacoemulsification-aspiration following the small anterior capsulotomy, EDTA or salts thereof can be effectively prevented from leaking out the capsular bag through the incised opening. EDTA or salts thereof does not leak out of the capsular bag so much to influence the intraocular tissues, and the lens epithelial cells which are difficult to sufficiently be removed even with the phacoemulsification-aspiration can be removed even with a low level of aspiration power.
• Retained lens materials are various substances remaining in the lens capsule during a cataract surgery, and the representative example of them is lens epithelial cells.
• compositions for debridement of retained lens materials comprising a viscoelastic material and EDTA or salts thereof both dissolved in a physiologically acceptable solution.
• the viscoelastic material is sodium hyaluronate.
• Preferable salts of EDTA in this invention are disodium salt, trisodium salt and tetrasodium salt, and a more preferable salt is disodium salt.
• the concentration of EDTA or salts thereof in the solution can be defined according to the binding strength of lens epithelial cells differing from patient to patient.
• the preferable concentration is 5 to 50 millimol/l, (hereinafter referred to as mM).
• viscoelastic material clinically applied high molecular materials can be used.
• materials are hyaluronic acid or salts thereof, methylcellulose, hydroxymethylcellulose, carboxyvinyl polymer, polyvinylpyrrolidone, polyvinylalcohol, polyacrylamide, kitin and collagen.
• sodium hyaluronate is more preferable.
• the above mentioned viscoelastic material is used in the form of physiologically acceptable solutions.
• the concentration of the viscoelastic material in the solutions is selected according to the desired viscosity, and usually 0.1 to 5% by weight, preferably 0.5 to 3.0% by weight.
• aqueous solution of sodium hyaluronate is widely used in ophthalmologic surgeries, and is preferable because of its protection effects on eye tissues.
• the molecular weight of sodium hyaluronate is not limited but selected according to the desired viscosity, and is in the range of about 600,000 to 4,000,000, preferably 800,000 to 3,000,000.
• the viscosity of sodium hyaluronate solution depends on its concentration and molecular weights, and is 2,000 to 200,000 cP, preferably 10,000 to 100,000 cP.
• the pH value of the preparations according to the present invention may be that ophthalmologically applied, and preferably in the range of 4 to 8.
• EDTA or salts thereof and the viscoelastic material such as sodium hyaluronate are dissolved in a physiologically acceptable solution to make the preparations, and if necessary pharmaceutically acceptable excipients, buffers, pH adjusting agent etc. can be added.
• physiologically acceptable solution examples include isotonic sodium chloride solution, distilled water for injection adjusted to physiological condition by adding isotonic agents such as sodium chloride and potassium chloride, and balanced salt solution (BSS).
• the preparation of this invention is injected through the capsular opening. Two minutes after the injection, the retained lens materials including lens epithelial cells are removed together with the preparation while the interior of the capsule being irrigated with an irrigation solution.
• the amount of the injected preparation can be selected according to the volume of the patient's lens capsule (about 0.2 ml).
• lens epithelial cells can be easily removed by injecting the composition according to the present invention into the capsular bag. Furthermore, leakage of EDTA or salts thereof from capsular opening can be effectively prevented by an application of EDTA or salts thereof with viscoelastic material.
• This invention offers a medical preparations which is effective in easy and complete debridement of retained lens materials such as lens epithelial cells by an aspiration during a cataract surgery.
• Disodium ethylenediaminetetraacetate was dissoloved in isotonic sodium chloride solution, and then to the solution was added sodium hyaluronate to make the preparations.
• Preparations of Formulas 11 to 14 were also made in the same manner.
• Disodium ethylenediaminetetraacetate was dissoloved in BSS, and then to the solution was added sodium hyaluronate to make the preparations.
• Preparations of Formula 16 was also made in the same manner.
• the piece was soaked for 2 minutes in isotonic sodium chloride solution containing disodium ethylenediaminetetraacetate and 1.5% by weight sodium hyaluronate (molecular weight: about 2 million).
• the piece was picked up by a pincette and washed with 10 ml of water by a syringe. The remaining extent of lens epithelial cells was observed by an inverted phase contrast microscope.
• a solution of disodium ethylenediaminetetraacetate and 1.5% sodium hyaluronate in isotonic sodium chloride solution was injectd into a lens capsule after an extraction of cataractous lens through a small anterior capsulotomy by endocapsular phacoemulsification procedure. After 2 minutes, lens endocapsular epithelial cells attached to the anterior capsule were aspirated off.
• a solution of disodium ethylenediaminetetraacetate (concentration: 10 mM) and 1.5% sodium hyaluronate in isotonic sodium chloride solution was injected into a lens capsule by the same manner as in Example 2. After 2 minutes, aqueous humor was sucked by a syringe and the amount of disodium ethylenediaminetetraacetate leaked into aqueous humor was measured.
• disodium ethylenediaminetetraacetate (concentration; 10 mM) dissolved in isotonic sodium chloride solution was used in the same manner as above mentioned procedure.
• the leakage rates (%) [(the amount of disodium ethylenediaminetetraacetate leaked into aqueous humor) ⁇ (the amount of injected disodium ethylenediaminetetraacetate) ⁇ 100] are shown in the following table.
• the leakage rate of the disodium ethylenediaminetetraacetate using sodium hyaluronate was nearly 0 in comparison with the fact that about 20% of the injected disodium ethylenediaminetetraacetate of the control was leaked, whereby the influences of the former on the peripheral intraocular tissues were negligible.

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• Health & Medical Sciences (AREA)
• Ophthalmology & Optometry (AREA)
• Veterinary Medicine (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Organic Chemistry (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 1991
  • 1991-06-28 EP EP91110799A patent/EP0464727B1/de not_active Expired - Lifetime
  • 1991-06-28 DK DK91110799.3T patent/DK0464727T3/da active
  • 1991-06-28 US US07/723,072 patent/US5204331A/en not_active Expired - Fee Related
  • 1991-06-28 DE DE69116010T patent/DE69116010T2/de not_active Expired - Fee Related
  • 1991-06-28 JP JP3157981A patent/JPH07116030B2/ja not_active Expired - Fee Related

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